# Administration of Nicotinamide Mononucleotide Mitigates the HIV Nef-Induced Metabolic and Pathological Changes in the Heart

## TL;DR

This study shows that nicotinamide mononucleotide (NMN) can reduce heart damage caused by HIV's Nef protein, offering a potential treatment for HIV-related heart disease.

## Contribution

The novel contribution is demonstrating that NMN treatment mitigates Nef-induced cardiac dysfunction and metabolic changes in a mouse model.

## Key findings

- Nef expression in cardiac tissue decreases NAD+ levels.
- NMN treatment improves autophagy and reduces the senescence marker Bcl2.
- NMN reduces heart fibrosis and may be a therapeutic target for HIV-associated cardiovascular disease.

## Abstract

Due to the application of antiretroviral therapy, HIV has become a manageable chronic disease, and people living with HIV/AIDS (PLWHA) experience several comorbidities, including cardiovascular disease. Although antiretroviral therapy suppresses the viral load to an undetectable level, HIV proteins can still be detected in the circulation and in different organs. In our previous study, we found that the expression of the Nef protein causes cardiac dysfunction and heart failure in a transgenic mouse model. We also observed inhibition of autophagy along with the upregulation of the senescence marker Bcl2. To further understand the metabolic changes related to Nef in cardiac tissue, we examined nicotinamide adenine dinucleotide (NAD) metabolism in the heart. Our metabolic study with cardiac tissue revealed that Nef expression decreases NAD+ levels in the heart. Additionally, we explored whether replenishing cellular NAD+ could be a potential therapeutic target for HIV-associated cardiovascular disease. Interestingly, our study found that NMN treatment can improve cellular autophagy, decrease the senescence marker Bcl2, and reduce fibrosis in the heart. Overall, our study suggests that NMN could serve as a promising therapeutic molecule for the treatment of HIV-associated cardiovascular comorbidities.